Hepatic Glutathione Homeostasis in the Rat: Efflux Accounts for Glutathione Turnover

Bernhard H. Lauterburg, James D. Adams, Jerry R. Mitchell – 1 July 1984 – Hepatic glutathione turnover and the efflux of glutathione from the liver into bile and blood were measured in male Sprague‐Dawley rats in vivo. In fed rats the efflux of glutathione into blood, calculated from the hepatic arteriovenous concentration gradient and hepatic blood flow, amounted to 12.4 ± 1.4 nmoles min.gm liver. Together with the excretion of glutathione into bile (3.4 ± 0.4 nmoles per min.gm liver) total efflux accounted for the hepatic turnover of glutathione of 15.2 ± 0.9 nmoles per min.gm liver.

Influence of Hydroxylation and Conjugation of Bile Salts on Their Membrane‐Damaging Properties‐Studies on Isolated Hepatocytes and Lipid Membrane Vesicles

Jürgen SchÖLmerich, Maria‐Sybille Becher, Karlheinz Schmidt, Rolf Schubert, Bernd Kremer, Susanne Feldhaus, Wolfgang Gerok – 1 July 1984 – To characterize the relative toxicity of different bile salts, isolated hepatocytes were incubated with different concentrations of one bile salt or with identical concentrations of different bile salts and their conjugates. Incubation lasted for 1 hr; samples were taken at different intervals and studied for enzyme release, urea synthesis and stimulation by glucagon, and by electron microscopy.

Sinusoidal Endothelial Cells from Normal Guinea Pig Liver: Isolation, Culture and Characterization

R. Gideon Shaw, Alice R. Johnson, Werner W. Schulz, Rainer N. Zahlten, Burton Combes – 1 July 1984 – Guinea pig nonparenchymal hepatic cells were isolated by enzymatic digestion and subsequent separation on a 17.5% metrizamide gradient. Endothelial cell and Kupffer cell‐enriched fractions were separated by centrifugal elutriation. Viability of both cell fractions was approximately 80%. Endothelial cells were cultured on a substratum of guinea pig liver collagen and 1% gelatin (1:1).

Disposition and Metabolism of Metronidazole in Patients with Liver Failure

Geoffrey Farrell, Judith Baird‐Lambert, Mara Cvejic, Neil Buchanan – 1 July 1984 – A pharmacokinetic study of metronidazole disposition was performed in 10 patients with severe liver disease, the majority of whom also had impaired renal function. Following a single intravenous dose, systemic clearance of metronidazole was decreased by 66% in patients compared with healthy controls (p < 0.001). The apparent volume of distribution for metronidazole was also decreased in patients (by 21%), but the greater effect on clearance resulted in the elimination half‐life being prolonged 152%.

Evidence for Valine Intolerance in Patients with Cirrhosis

Peter Schauder, Karsten SchrÖDer, Lothar Herbertz, Klaus Langer, Ulrich Langenbeck – 1 July 1984 – Valine (62.5 mg per kg), leucine (70 mg per kg) and equal amounts of the calcium salts of the corresponding keto acids, i.e., α1‐ketoisovaleric acid (KIVA) and α1‐ketoisocaproic acid (KICA) were orally administered to patients with cirrhosis and to control subjects.Valine or leucine ingestion increased serum valine and leucine levels and the corresponding keto acids, KIVA and KICA, in cirrhotics and controls.

Does Primary Biliary Cirrhosis in Men Differ from Primary Biliary Cirrhosis in Women?

Lawrence R. Rubel, Lionel Rabin, Leonard B. Seeff, Harvey Licht, Brenda A. Cuccherini – 1 July 1984 – Primary biliary cirrhosis is infrequently diagnosed in men, so that the clinical, biochemical and histopathological spectrum of this disease in men has not been evaluated. Therefore, we studied 30 men who had a histological diagnosis of primary biliary cirrhosis and had positive tests for antimitochondrial antibodies. Five patients had no hepatobiliary symptoms, and two of these patients had neither biochemical nor histological evidence of cholestasis.

Enhancement by Secretin of the Apparently Maximal Hepatic Transport of Bilirubin in the Rat

Giovanni L. Ricci, Roger Michiels, Johan Fevery, Jan De Groote – 1 July 1984 – The effect of secretin (0.4 C.U. per hr per 100 gm body weight) on bile flow and the apparent maximal hepatic transport of bilirubin (Tm) was investigated in the rat. When secretin was administered during an already established bilirubin‐Tm condition, it increased bile flow and bilirubin‐Tm by 15 to 20% over a 30‐ to 50‐min period. Enhancement of bilirubin output correlated with augmented flow and was sustained by an increased rate of excretion of monoglucuronides.

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